The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS h...The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS have been extensively studied and routinely treated with autografts, acellular nerve allografts, conduits, wraps, and nerve transfers. In contrast, segmental-loss peripheral nerve injuries, in which one or more branch points are ablated so that there are three or more nerve endings, present additional complications that have not been rigorously studied or documented. This review discusses:(1) the branched anatomy of the peripheral nervous system,(2) case reports describing how peripheral nerve injuries with branched ablations have been surgically managed,(3) factors known to influence regeneration through branched nerve structures,(4) techniques and models of branched peripheral nerve injuries in animal models, and(5) conclusions regarding outcome measures and studies needed to improve understanding of regeneration through ablated branched structures of the peripheral nervous system.展开更多
This review addresses the accumulating evidence that live(not decellularized)allogeneic peripheral nerves are functionally and immunologically peculiar in comparison with many other transplanted allogeneic tissues.Thi...This review addresses the accumulating evidence that live(not decellularized)allogeneic peripheral nerves are functionally and immunologically peculiar in comparison with many other transplanted allogeneic tissues.This is relevant because live peripheral nerve allografts are very effective at promoting recovery after segmental peripheral nerve injury via axonal regeneration and axon fusion.Understanding the immunological peculiarities of peripheral nerve allografts may also be of interest to the field of transplantation in general.Three topics are addressed:The first discusses peripheral nerve injury and the potential utility of peripheral nerve allografts for bridging segmental peripheral nerve defects via axon fusion and axon regeneration.The second reviews evidence that peripheral nerve allografts elicit a more gradual and less severe host immune response allowing for prolonged survival and function of allogeneic peripheral nerve cells and structures.Lastly,potential mechanisms that may account for the immunological differences of peripheral nerve allografts are discussed.展开更多
Objective: To evaluate the clinical safety and efficacy of the retrograde perfusion technique in kidney transplantation.Methods: Between January 2001 and June 2011, 24 cases of kidney transplantation with kidneys perf...Objective: To evaluate the clinical safety and efficacy of the retrograde perfusion technique in kidney transplantation.Methods: Between January 2001 and June 2011, 24 cases of kidney transplantation with kidneys perfused using the retrograde perfusion technique due to renal artery variations or injury were selected as the observation group (retrograde perfussion roup, RP group).Twenty-two cases of kidney transplantation via conventional perfusion were chosen as the control group (antegrade perfussion group, AP group).There were no statistically significant differences in donor data between the two groups.Cold ischemia time, warm ischemia time, renal perfusion time, amount of perfusion fluid, acute renal tubular necrosis, wound infection, urinary fistula, graft kidney function, and the 1-year, 3-year, and 5-year survival rates for the grafted kidney in both groups were observed and recorded.Results: The kidney perfusion time was shorter in the RP group than that in the AP group (3.14 ± 1.00 vs.5.02 ± 1.15 min, P =0.030).There were 10 cases of acute renal tubule necrosis in the RP group and 5 in the AP group.The length of hospital stay was 40 ± 14 d in the RP group and 25 ± 12 d in the AP group.The follow-up time was 3.5-8.5 years (mean 6.25 years).The 1-, 3-, and 5-year survival rates for the grafted kidney were 95.8％, 75.5％, and 65.5％ in the RP group and 97.1％, 82.5％, and 68.4％ in the AP group, respectively (P＞0.05).Conclusions: This study indicates that retrograde perfusion is safe and practicable for cadaveric kidney harvesting and can be regarded as a better alternative or remedial measure for a poorly perfused kidney due to vascular deformity or injury.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).展开更多
AIM:To evaluate pre-lung transplant acid reflux on p H-testing vs corresponding bolus reflux on multichannel intraluminal impedance(MII) to predict early allograft injury.METHODS:This was a retrospective cohort study ...AIM:To evaluate pre-lung transplant acid reflux on p H-testing vs corresponding bolus reflux on multichannel intraluminal impedance(MII) to predict early allograft injury.METHODS:This was a retrospective cohort study of lung transplant recipients who underwent pretransplant combined MII-p H-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-p H testing and early allograft injury. Area under the receiver operating characteristic(ROC) curve(c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six p H-testing parameters and their corresponding MIImeasures were specified a priori. The p H parameters were upright,recumbent,and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright,recumbent,and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time.RESULTS:Thirty-two subjects(47% men,mean age:55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis(46.9%) repres e n t e d t h e m o s t c o m m o n p u l m o n a r y d i a g n o s i s leading to transplantation. Baseline demographics,pre-transplant cardiopulmonary function,number of lungs transplanted(unilateral vs bilateral),and posttransplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve,or c-statistic,of each acid reflux parameter on pre-transplant p H-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition,the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux:overall reflux exposure(HR = 1.18,95%CI:1.01-1.36,P = 展开更多
Direct coaptation of contralateral C7 to the upper trunk could avoid the interposition of nerve grafts. We have successfully shortened the gap and graft lengths, and even achieved direct coaptation. However, direct re...Direct coaptation of contralateral C7 to the upper trunk could avoid the interposition of nerve grafts. We have successfully shortened the gap and graft lengths, and even achieved direct coaptation. However, direct repair can only be performed in some selected cases, and partial procedures still require autografts, which are the gold standard for repairing neurologic defects. As symptoms often occur after autografting, human acellular nerve allografts have been used to avoid concomitant symptoms. This study investigated the quality of shoulder abduction and elbow flexion following direct repair and acellular allografting to evaluate issues requiring attention for brachial plexus injury repair. Fifty-one brachial plexus injury patients in the surgical database were eligible for this retrospective study. Patients were divided into two groups according to different surgical methods. Direct repair was performed in 27 patients, while acellular nerve allografts were used to bridge the gap between the contralateral C7 nerve root and upper trunk in 24 patients. The length of the harvested contralateral C7 nerve root was measured intraoperatively. Deltoid and biceps muscle strength, and degrees of shoulder abduction and elbow flexion were examined according to the British Medical Research Council scoring system;meaningful recovery was defined as M3–M5. Lengths of anterior and posterior divisions of the contralateral C7 in the direct repair group were 7.64 ± 0.69 mm and 7.55 ± 0.69 mm, respectively, and in the acellular nerve allografts group were 6.46 ± 0.58 mm and 6.43 ± 0.59 mm, respectively. After a minimum of 4-year follow-up, meaningful recoveries of deltoid and biceps muscles in the direct repair group were 88.89% and 85.19%, respectively, while they were 70.83% and 66.67% in the acellular nerve allografts group. Time to C5/C6 reinnervation was shorter in the direct repair group compared with the acellular nerve allografts group. Direct repair facilitated the restoration of shoulder abduction and elbow flexion展开更多
Schwann cell proliferation in peripheral nerve injury(PNI)enhances axonal regeneration compared to central nerve injury.However,even in PNI,long-term nerve damage without repair induces degeneration of neuromuscular j...Schwann cell proliferation in peripheral nerve injury(PNI)enhances axonal regeneration compared to central nerve injury.However,even in PNI,long-term nerve damage without repair induces degeneration of neuromuscular junctions(NMJs),and muscle atrophy results in irreversible dysfunction.The peripheral regeneration of motor axons depends on the duration of skeletal muscle denervation.To overcome this difficulty in nerve regeneration,detailed mechanisms should be determined for not only Schwann cells but also NMJ degeneration after PNI and regeneration after nerve repair.Here,we examined motor axon denervation in the tibialis anterior muscle after peroneal nerve transection in thy1-YFP mice and regeneration with nerve reconstruction using allografts.The number of NMJs in the tibialis anterior muscle was maintained up to 4 weeks and then decreased at 6 weeks after injury.In contrast,the number of Schwann cells showed a stepwise decline and then reached a plateau at 6 weeks after injury.For regeneration,we reconstructed the degenerated nerve with an allograft at 4 and 6 weeks after injury,and evaluated functional and histological outcomes for 10 to 12 weeks after grafting.A higher number of pretzel-shaped NMJs in the tibialis anterior muscle and better functional recovery were observed in mice with a 4-week delay in surgery than in those with a 6-week delay.Nerve repair within 4 weeks after PNI is necessary for successful recovery in mice.Prevention of synaptic acetylcholine receptor degeneration may play a key role in peripheral nerve regeneration.All animal experiments were approved by the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University on 5 July 2017,30 March 2018,and 15 May 2019(A2017-311C,A2018-297A,and A2019-248A),respectively.展开更多
AIM To evaluate and compare the outcomes of kidney transplant(KT) from deceased donors among standard criteria, acute kidney injury(AKI) and expanded criteria donors(ECDs). METHODS This retrospective study included 11...AIM To evaluate and compare the outcomes of kidney transplant(KT) from deceased donors among standard criteria, acute kidney injury(AKI) and expanded criteria donors(ECDs). METHODS This retrospective study included 111 deceased donor kidney transplant recipients(DDKT). Deceased donors were classified as standard criteria donor(SCD), AKI donor and ECD. AKI was diagnosed and classified based on change of serum Cr by acute kidney injury network(AKIN) criteria. Primary outcome was one-year estimated glomerular filtration rate(eG FR) calculated from Cr by CKD-EPI. Multivariate regression analysis was done by adjusting factors such as type of DDKT, %Panel-reactive antibodies, cold ischemic time, the presence of delayed graft function and the use of induction therapy. Significantfactors that can affect the primary outcomes were then identified. RESULTS ECD group had a significantly lower eG FR at one year(33.9 ± 17.3 mL /min) when compared with AKI group(56.6 ± 23.9) and SCD group(63.6 ± 19.9)(P < 0.001). For AKI group, one-year eG FR was also indifferent among AKIN stage 1, 2 or 3. Patients with AKIN stage 3 had progressive increase of eG FR from 49.6 ± 27.2 at discharge to 61.9 ± 29.0 mL /min at one year. From Kaplan-Meier analysis, AKI donor showed better two-year graft survival than ECD(100% vs 88.5%, P = 0.006). Interestingly, AKI group had a stable eG FR at one and two year. The two-year eG FR of AKI group was not significantly different from SCD group(56.6 ± 24.5 mL /min vs 58.6 ± 23.2 mL /min, P = 0.65). CONCLUSION Kidney transplantations from deceased donors with variable stage of acute kidney injuries were associated with favorable two-year allograft function. The outcomes were comparable with KT from SCD. This information supports the option that deceased donors with AKI are an important source of organ for kidney transplantation even in the presence of stage 3 AKI.展开更多
基金University of Wyoming Startup funds,United States Department of Defense,No. W81XWH-17-1-0402 (to JSB)the University of Wyoming Sensory Biology COBRE under National Institutes of Health (NIH),No. 5P20GM121310-02 (to JSB)+2 种基金the National Institute of General Medical Sciences of the NIH,No. P20GM103432 (to JSB)DOD AFIRM III,No. W81XWH-20-2-0029 (to GDB)a Lone Star Paralysis Foundation gi?t (to GDB)。
文摘The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS have been extensively studied and routinely treated with autografts, acellular nerve allografts, conduits, wraps, and nerve transfers. In contrast, segmental-loss peripheral nerve injuries, in which one or more branch points are ablated so that there are three or more nerve endings, present additional complications that have not been rigorously studied or documented. This review discusses:(1) the branched anatomy of the peripheral nervous system,(2) case reports describing how peripheral nerve injuries with branched ablations have been surgically managed,(3) factors known to influence regeneration through branched nerve structures,(4) techniques and models of branched peripheral nerve injuries in animal models, and(5) conclusions regarding outcome measures and studies needed to improve understanding of regeneration through ablated branched structures of the peripheral nervous system.
基金supported by University of Wyoming Startup Funds,United States Department of Defense,grant No.W81XWH-17-1-0402the University of Wyoming Sensory Biology COBRE under National Institutes of Health(NIH),award number 5P20GM121310-02+2 种基金the National Institute of General Medical Sciences of the NIH under Award Number P20GM103432(to JSB)the Lone Star Paralysis Foundation,NIH R01NS081063Department of Defense award W81XWH-19-2-0054 to GDB。
文摘This review addresses the accumulating evidence that live(not decellularized)allogeneic peripheral nerves are functionally and immunologically peculiar in comparison with many other transplanted allogeneic tissues.This is relevant because live peripheral nerve allografts are very effective at promoting recovery after segmental peripheral nerve injury via axonal regeneration and axon fusion.Understanding the immunological peculiarities of peripheral nerve allografts may also be of interest to the field of transplantation in general.Three topics are addressed:The first discusses peripheral nerve injury and the potential utility of peripheral nerve allografts for bridging segmental peripheral nerve defects via axon fusion and axon regeneration.The second reviews evidence that peripheral nerve allografts elicit a more gradual and less severe host immune response allowing for prolonged survival and function of allogeneic peripheral nerve cells and structures.Lastly,potential mechanisms that may account for the immunological differences of peripheral nerve allografts are discussed.
文摘Objective: To evaluate the clinical safety and efficacy of the retrograde perfusion technique in kidney transplantation.Methods: Between January 2001 and June 2011, 24 cases of kidney transplantation with kidneys perfused using the retrograde perfusion technique due to renal artery variations or injury were selected as the observation group (retrograde perfussion roup, RP group).Twenty-two cases of kidney transplantation via conventional perfusion were chosen as the control group (antegrade perfussion group, AP group).There were no statistically significant differences in donor data between the two groups.Cold ischemia time, warm ischemia time, renal perfusion time, amount of perfusion fluid, acute renal tubular necrosis, wound infection, urinary fistula, graft kidney function, and the 1-year, 3-year, and 5-year survival rates for the grafted kidney in both groups were observed and recorded.Results: The kidney perfusion time was shorter in the RP group than that in the AP group (3.14 ± 1.00 vs.5.02 ± 1.15 min, P =0.030).There were 10 cases of acute renal tubule necrosis in the RP group and 5 in the AP group.The length of hospital stay was 40 ± 14 d in the RP group and 25 ± 12 d in the AP group.The follow-up time was 3.5-8.5 years (mean 6.25 years).The 1-, 3-, and 5-year survival rates for the grafted kidney were 95.8％, 75.5％, and 65.5％ in the RP group and 97.1％, 82.5％, and 68.4％ in the AP group, respectively (P＞0.05).Conclusions: This study indicates that retrograde perfusion is safe and practicable for cadaveric kidney harvesting and can be regarded as a better alternative or remedial measure for a poorly perfused kidney due to vascular deformity or injury.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).
文摘AIM:To evaluate pre-lung transplant acid reflux on p H-testing vs corresponding bolus reflux on multichannel intraluminal impedance(MII) to predict early allograft injury.METHODS:This was a retrospective cohort study of lung transplant recipients who underwent pretransplant combined MII-p H-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-p H testing and early allograft injury. Area under the receiver operating characteristic(ROC) curve(c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six p H-testing parameters and their corresponding MIImeasures were specified a priori. The p H parameters were upright,recumbent,and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright,recumbent,and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time.RESULTS:Thirty-two subjects(47% men,mean age:55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis(46.9%) repres e n t e d t h e m o s t c o m m o n p u l m o n a r y d i a g n o s i s leading to transplantation. Baseline demographics,pre-transplant cardiopulmonary function,number of lungs transplanted(unilateral vs bilateral),and posttransplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve,or c-statistic,of each acid reflux parameter on pre-transplant p H-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition,the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux:overall reflux exposure(HR = 1.18,95%CI:1.01-1.36,P =
基金supported by the National Natural Science Foundation of China,No.81572130(to LQG)and 81601057(to JTY)the National Key Research and Development Plan of China,No.2016YFC1101603(to XLL)the Natural Science Foundation of Guangdong Province of China,No.2015A030310350(to JTY)
文摘Direct coaptation of contralateral C7 to the upper trunk could avoid the interposition of nerve grafts. We have successfully shortened the gap and graft lengths, and even achieved direct coaptation. However, direct repair can only be performed in some selected cases, and partial procedures still require autografts, which are the gold standard for repairing neurologic defects. As symptoms often occur after autografting, human acellular nerve allografts have been used to avoid concomitant symptoms. This study investigated the quality of shoulder abduction and elbow flexion following direct repair and acellular allografting to evaluate issues requiring attention for brachial plexus injury repair. Fifty-one brachial plexus injury patients in the surgical database were eligible for this retrospective study. Patients were divided into two groups according to different surgical methods. Direct repair was performed in 27 patients, while acellular nerve allografts were used to bridge the gap between the contralateral C7 nerve root and upper trunk in 24 patients. The length of the harvested contralateral C7 nerve root was measured intraoperatively. Deltoid and biceps muscle strength, and degrees of shoulder abduction and elbow flexion were examined according to the British Medical Research Council scoring system;meaningful recovery was defined as M3–M5. Lengths of anterior and posterior divisions of the contralateral C7 in the direct repair group were 7.64 ± 0.69 mm and 7.55 ± 0.69 mm, respectively, and in the acellular nerve allografts group were 6.46 ± 0.58 mm and 6.43 ± 0.59 mm, respectively. After a minimum of 4-year follow-up, meaningful recoveries of deltoid and biceps muscles in the direct repair group were 88.89% and 85.19%, respectively, while they were 70.83% and 66.67% in the acellular nerve allografts group. Time to C5/C6 reinnervation was shorter in the direct repair group compared with the acellular nerve allografts group. Direct repair facilitated the restoration of shoulder abduction and elbow flexion
基金supported by the Japan Society for the Promotion of Science KAKENHI(Grants 26462230 [to YM] and 16K10813 [to ME])grants from the Japan Student Services Organization(JASSO)
文摘Schwann cell proliferation in peripheral nerve injury(PNI)enhances axonal regeneration compared to central nerve injury.However,even in PNI,long-term nerve damage without repair induces degeneration of neuromuscular junctions(NMJs),and muscle atrophy results in irreversible dysfunction.The peripheral regeneration of motor axons depends on the duration of skeletal muscle denervation.To overcome this difficulty in nerve regeneration,detailed mechanisms should be determined for not only Schwann cells but also NMJ degeneration after PNI and regeneration after nerve repair.Here,we examined motor axon denervation in the tibialis anterior muscle after peroneal nerve transection in thy1-YFP mice and regeneration with nerve reconstruction using allografts.The number of NMJs in the tibialis anterior muscle was maintained up to 4 weeks and then decreased at 6 weeks after injury.In contrast,the number of Schwann cells showed a stepwise decline and then reached a plateau at 6 weeks after injury.For regeneration,we reconstructed the degenerated nerve with an allograft at 4 and 6 weeks after injury,and evaluated functional and histological outcomes for 10 to 12 weeks after grafting.A higher number of pretzel-shaped NMJs in the tibialis anterior muscle and better functional recovery were observed in mice with a 4-week delay in surgery than in those with a 6-week delay.Nerve repair within 4 weeks after PNI is necessary for successful recovery in mice.Prevention of synaptic acetylcholine receptor degeneration may play a key role in peripheral nerve regeneration.All animal experiments were approved by the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University on 5 July 2017,30 March 2018,and 15 May 2019(A2017-311C,A2018-297A,and A2019-248A),respectively.
文摘AIM To evaluate and compare the outcomes of kidney transplant(KT) from deceased donors among standard criteria, acute kidney injury(AKI) and expanded criteria donors(ECDs). METHODS This retrospective study included 111 deceased donor kidney transplant recipients(DDKT). Deceased donors were classified as standard criteria donor(SCD), AKI donor and ECD. AKI was diagnosed and classified based on change of serum Cr by acute kidney injury network(AKIN) criteria. Primary outcome was one-year estimated glomerular filtration rate(eG FR) calculated from Cr by CKD-EPI. Multivariate regression analysis was done by adjusting factors such as type of DDKT, %Panel-reactive antibodies, cold ischemic time, the presence of delayed graft function and the use of induction therapy. Significantfactors that can affect the primary outcomes were then identified. RESULTS ECD group had a significantly lower eG FR at one year(33.9 ± 17.3 mL /min) when compared with AKI group(56.6 ± 23.9) and SCD group(63.6 ± 19.9)(P < 0.001). For AKI group, one-year eG FR was also indifferent among AKIN stage 1, 2 or 3. Patients with AKIN stage 3 had progressive increase of eG FR from 49.6 ± 27.2 at discharge to 61.9 ± 29.0 mL /min at one year. From Kaplan-Meier analysis, AKI donor showed better two-year graft survival than ECD(100% vs 88.5%, P = 0.006). Interestingly, AKI group had a stable eG FR at one and two year. The two-year eG FR of AKI group was not significantly different from SCD group(56.6 ± 24.5 mL /min vs 58.6 ± 23.2 mL /min, P = 0.65). CONCLUSION Kidney transplantations from deceased donors with variable stage of acute kidney injuries were associated with favorable two-year allograft function. The outcomes were comparable with KT from SCD. This information supports the option that deceased donors with AKI are an important source of organ for kidney transplantation even in the presence of stage 3 AKI.
